Method of and means for preparing medicinal and anesthetic solutions



Feb. 9 1926;

. :A. E. SMITH METHOD OF AND MEANS FOR PREP mm MEDICINAL AND ANIZSTHETIC SOLUTIONS Filed Dec. 16,1922

Patented Feb. 9, 1926.

UNITE-D STAT ES arana" rrros.

ARTHUR E. SMITH, OF PITTSBURG, KANSAS, ASSIGNOR T0 CLAUDE 1L. SMITH, OF PITTSBUEG, KANSAS.

METHOD on Am) mnansr'onrnnrnnme MEDICINAL AND anzssrnnriosonnrions,

Application flled December To all whom it may concern:

Be it known that I, ARTHUR E. SMITH, a citizen of the United States, residing at Pittsburg, in the county of Crawford and State of Kansas, have invented certain new and useful Improvements in and Means for Preparing Medicinal and Anaesthetic Solutions, of which the following a specification.

This invention relates to a. method oi and means for preparing medicinal and anaesthetic packages. The inv'entionis of particular valve in the preparation or anaesthetic solutions used indental nerve blocking work but its usefulness extends beyond that particular field, as will be presently apparent.

United States Patent No. 1,2et3349, issued to me on the 16th day of October, 1917, described a nerve blocking tablet, having combined therein the necessary chlorides to make Ringers solution, a vaso constricting agent, such as suprarenin or adrenalin, for example, and an anaesthetic, such as novocain for example, all in such proportions that when a tablet is-disso'lved in a definite and predetermined amount of distilled water a solution isotonic to the blood is produced. However, it has been found that it has not becna simple matter "for the dentistto produce required, absolutely pure distilled water in accurate quantity and to lteep 1ttrce of contamination until used. Particular- 1y is this true if the condition of the patient is such as to require the dentist to'treat the patient in the home, where no'oiiic'e or laboratory appliances are available.

It is, therefore, a primary object of the present invention to combine, asa unit, the necessary amount of pure distilled Water and the necessary ingredients to be mixed therewith and to maintain them separate until the time of use arrives, the container and the separating means being of such a nature that mixing of the water other ingredients may be effected with ease and dispatch and without subjecting the resultant solution to the air, until the moment of use arrives.

In order that the advantages of the forward step made in the art by "this inven tion, may be better appreciated, it is pointed out that to secure safe and certain results in nerve blocking anaesthesia the following must be observed Methods of.

and the 16, 1922. Serial No. (307,391.

First: 'For safety and the best results the solution must be fresh at the time of use. In other Words the Water and the other ingredients must not be brought together until the time of use arrives, or substantially so. The importanceo't having the solution fresh at the time of use is well recognized in the-dental and medical professions and in the literature relating thereto. On page .463 of Prinzs textbook entilted Dental Materia Medicaand Therapeutics, third edition, the following is found:

The practitioner is especially cautioned in regard to the use of local anaesthetics in the form of ready made solutions. Solutions of cocain, even when rendered sterile by "fractional sterilization, will not remain so after the contents of the bottle are exposed to the air for a short time. Ready made solutions that are sold in the shops under more or less fanciful names require still greater precautions. The recently enacted pure food and drug act requires that all solutions containing cocain, casein, and other similar alkaloids, must be labeled. Most of the many, so called, safe and reliable anaesthetics found in the market, contain cocain-orits substitute in various-quantities. The addition of adrenalinto a ready made solution not only destroys this alkaloid in a very short time, but the product of its decomposition with the decomposed cooain makes the solution still more dangerous. The printed tormulas that accompany many of the ready made solutions of local anaesthetics frequently showan utter disre- ,g arcl of the pharmacologic action ot the individual ingredients which forces us to conclude that they are a slur on the intelligence oft-he practitioner who uses such compounds.

Quoting Fischer from his textbook en= titled Local Anaesthesia in Dentistry, page 48 in l9l-al'edition,

Synthetic supra-re'nin is stable only to a limited degree after the bottle 'has'once been opened; for this reason the transferring into another vessel of the quantity required in every case, as recommended by Seidcl, seems impracticable. In private practice it is best to make a fresh solution from tablets, as cases present themselves. The very convenlent tablets, as 'Braun writes,"arepreterable to any other tornroi dispensing alkaloids used for medical purposes. This is especially true of unstable drugs like suprarenin which, in dry tablet form, keep for a long time.

Same author from page 53:

Numerous solutions in the market not only contain admixtures of highly toxic drugs, but also lack sufficient neutrality; in other words, they are not isotonic but hetero tonic. Novocain-suprarenin solutions which are intended for injection must always be of the purest quality; they must be crystal clear and not contain any admixtures nor must they have come in contact with any impurities during the process of preparation.

Same author from page 55: c p

F or the requirements of daily practice it seemed expedient to dispense novocainsuprarenin in ampules so as to offer the solution ready for use in convenient form. Our experiences with these ampules, however, induce us to give the preference to solutions freshly made'from tablets, for the present at least. The ampule solution decomposes more quickly and its stability depends upon the conditions of temperature and light under which it is preserved. Suprarenal extract is not stable for any len 'th of time when in liquid union with novocain.

Same author page ll:

The preparations marketed in ampules are somewhat untrustworthy. according to recent opinions, because their stability is a limited one. For this reason freshly made solutions are absolutely preferable to all stock solutions,

Second: The resultant solution must be isotonic to the blood; i. e., the amount of water used must be in such proportion to the chlorides which form the Rina'ers solution that the solution will not be hypertonic, or concentrated, so as to contain more of the chlorides than are found in an equal amount of blood. It is necessary in the use of a local anaesthetic solution of this nature to have it conform to the chlorides (salts) in the blood. If the solution is not isotonic. then the osmotic pressure. of the solution will be different from that of the surround ing tissues and will cause pathological changes in the blood and other tissues. that are highly undesirable. A local anaesthetic solution when injected should not produce pathologic tissue changes and should conform to the physical and physiological laws of the living cells comprising the various tissues.

Third: The water used must be absolutely pure. distilled water, to begin with and must be maintained in a sterile and uncontaminated condition.

Broadly speaking the invention consists of enclosing within any suitable container any two or more substances one of which at least is liquid and separating one or more of the substances from the other or others, until the time of use arrives. by a fusible wall of a material which will retain its form and solidity under ordinary temperatures butmay be melted at higher temperatures. lVhen the time of use arrives this separating wall is melted by the application of heat and the contents of the package or container are mixed, and the package is opened, and its contents used.

I preferably embody the foregoing invention in the form of an ampule of glass and in the particular embodiment of the invention illustrated in the accompanying drawing some of the ingredients, whether in the form of apowder, liquid, tablet or otherwise, are enclosed within a capsule of chemically pure paraffin by which the contents of the capsule are maintained in their original state until the time of use arrives. The enclosing of the constituent elements of the package in an ampule not only protects its contents from contact with the outside air but, since these ampules are commonly sealed under a vacuum, it insures that no air will be in contact with the substances within the ampule during the time that the article is in stock.

In the accompanying drawing:

Fig. 1 is a view partly in side elevation and partly in section of an ampule embodying one form of the invention and illustratino' the same before the ampule is subjected to neat;

Fig. 2 illustrates the ampule after having been subjected to heat and cooled as hereinafter described; and

Fig. 3 is a view of the empty package after the contents have been removed for use.

In carrying out the invention, in the particular form illustrated in the drawing, I provide an ampnle 5, of glass, which may be of any desired color and free of alkali. This ampule is provided with a neck extension 6 which may be readily broken therefrom after being slightly nicked with a small file. A capsule 7, of chemically pure paraflin, receives one or more tablets, indicated at 8, and the body of the ampule receives distilled water 9, which is sterile and free of all foreign substances. After the water and capsule have been placed in the ampule, the ainpule is sealed, under a vacuum, at its neck portion 6, by fusing the glass together in a manner well known in the art. lVhile I have stated that the capsule 7v contains a tablet or tablets it is manifest that it may receive the necessary material in powder or liquid form. here the ainpule is to be used in nerve blocking work the material contained within the capsule 7 will contain, as before stated, the necessary chlorides t0 produce a Ringers solution, a-vaso constricting ingredient and an anaesthetic, and these will be in such proportions to the amount of distilled water contained within the ampule that the resultant solution will be isotonic to the blood. However, if an anaesthetic solution of a different typefrom that employed in nerve blocking work is desired, the invention is still of utility, since any suitable material may be placed within the capsule 7 and mixed with the water only when the time of use arrives, as will be presently set forth. In other words, the invention, while being of particular utility in connection with dental nerve blocking work, is not necessarily limited thereto, but has a wide range of usefulness, since it pro vides means to enable any physician or dentist to easily and quickly prepare solutions of many kinds which will have the advantage of being freshly prepared from fresh, uncontaminated ingredients, irrespective of what the particular material contained within the capsule 7 may be.

When the time of use arrives, the ampule shown in the drawing; is placed in water in a sterilizer and boiled or held in running hot water, with the result that the paraffin capsule is melted and the water comes into contact with the tablets or other contents of the capsule. Thus a fresh Ringers'solution is prepared at the same time that the local iilliBStllQtlC and the vase-constricting in-- gred'zents are dissolving. The resultant solution is isotonic to the blood because, since the ainpule is sealed, none of the distilled water can be lost by evaporation or spilling. Since the contents are tightly sealed in the ampule, the ainpule may be taken to the home of the patient and there boiled, with safety, in any domestic vessel. 7

After the ampule has been boiled for a suliicient length of time it is placed upside down or in the position illustrated in Fig. 2, in a glass of cold water, or is held in cold running;- water, or otherwise chilled, whereupon the pararlin solidifies and forms a lump at the upper end of the ampule, being completely separated from the solution. The paracli'in being of a lesser specific gravity than water will float on the surface of the water and will solidify when the tempera ture is lowered. Then the ampule is turned right side up, its neck portion 6 is nicked with a small iile and the neck portion is broken oil. The contents may then be drawn into the hypodermic syringe, without ever having had the solution leave its original container. it is well known that the pouring; of solutions of this character from one container into another otters a chance of contamination. 'l'he boiling of the aim pule iuthe sterilizer can take place at the same time that the instruments to be used in the operation are being sterilized. Thus time is saved. V hen the ainpule is placed in cold water after it is removed fromthe sterilizer the solution is quickly cooled. Consequently little time, or even no time,

is lost. These-me action which congeals or solidifies the paraffin, cools the hot solution to the temperature of the body, so that it can be injected. Under the old method, where the solution was prepared in a porcelain cup or crucible, considerable time was lost while waiting for the solution to cool.

While, as before stated, the methodand means herein described are of utility in preparing medicinal solutions in general, I desire to make it clear that the contents of the capsule, when the resultant solution is to be used in dental nerve blocking work, consists of an anaesthetic of a suitable charac ter, such as novocain .or anocain, a vasoconstricting ingredient, which may be suprarenin or adrenalin hydro-chloride and a chloride or chlorides, in such proportion as to render the resulting solution isotonic to the blood. All of the chlorides of Ringers solution may be used or any of the chlorides which are used in making a Ringer solution. For example, sodium chloride alone may be employed, but the best results are secured by employing all the Ringer chlorides.

While I have described a capsule of paraffin as the separating fusible medium, the non-liquid constituent may be in the form of a single tablet of the proper size and this may be dipped and redipped in melted para'liin until it is covered and encased within a Waterproof wall of paraflin. Furthermore, other material than parafiin may be used. It is only necessary that the material be of a nature to retain its form under ordinary temperatures, be fusible under the application of heat and be nonmiscible with the contents of the ampule.

I desire to lay particular stress upon the fact that the invention is not limited to usein the preparation of medicinal packages containing anaesthetics, but that it has a wide range of usefulness in packaging any medicinal preparation which it is desired to mix fresh at the time of use. For example, digitalisis susceptible to deterioration and it is highly desirable in the use of this drug that it be fresnly mixed with pure distilled water at the time of use. Thus an ampule containing a body of distilled water and a capsule containing; digitalis would come within the scope of the inv..rtion and be of great utility. There are many other drugs which in concentrated form retain their strength and other properties indefinitely but which deteriorate when mixed with distilled water or other ingredients. Furthcn more it is within the scope of the invention to use other liquids than distilled water as the main body of liquid. For example, the chlorides of Ringers solution might be mixed with the distilled water and this constitute the main body of liquid and the capsule contain tablets comprising only the anaesthetic and suprarenin; or the suprarenin (vaso-constricting agent) might be contained alone in the capsule, while having the water contain the anaesthetic and the Ringers constituents. Any of these modifications are contemplated by me and are within the scope of the invention.

It is to be understood that the invention is not limited to the use of any specific form of container or shape of ampule, since these may be varied within wide ranges and still come within the scope of the invention defined by the following claims.

Having described by invention what I claim is:

l. The herein described method of putting up the ingredients of an anaesthetic solution which consists of placing in a container liquid and non-liquid constituents, and separating them by a wall, fusible at a point ma terially below the fusion point of the material of the container.

2. The herein described method of putting up the ingredients of an anaesthetic solution which consists of placing in a container liquid and non-liquid constituents and enveloping the non-liquid constituent by a water-proof wall, fusible at a point ma terially below the fusion point of the material of the container.

3. The herein described method of putting up the ingredients of an anaesthetic solution which consists of placing in a water-proof container distilled water and a non-liquid constituent in predetermined proportions and enveloping the non-liquid constituent with a water-proof wall of material fusible at a point materially below the fusion point of the material of the container.

4. The herein described method of putting 'up the ingredients of an anzesthetic solution which consists of placing in a water-tight container distilled water and a non-liquid constituent in predetermined proportions and enveloping. the non-liquid constituent with a wall of chemically pure paraflin.

5. The herein described method of putting up the ingredients of an anaesthetic solution which consists of placing distilled water and a non-liquid ingredient in a hermetically sealed container, the non-liquid ingredient being enclosed in a capsule of pure parafiin.

G. In combination a sealed container of glass containing a liquid ingredient and a non-liquid ingredient, the non-liquid ingredient. being separated from the liquid ingredient by a water-proof wall fusible at a point materially below the fusion point of the material of the container.

7. In combination a sealed glass container consisting of a liquid ingredient and a nonliquid ingredient, the non-liquid ingredient being separated from the liquid ingredient by a wall of chemically pure paraffin fusible when the container is subjected to a temperature materially above normal.

8. In combination a sealed glass container containing distilled water and solid ingredients comprising one or more of the chlorides of Ringers solution, a vaso-constricting ingredient and an anaesthetic, the solid c0ntents of the containerbeing separated from the distilled water by a wall of material fusible when the container is subjected to boiling and which will solidify and separate from the distilled water at ordinary temperature.

9. In combination a sealed glass ampule containing distilled water and a capsule of a material fusible at a point materially below the fusion point of the material of the ampule, said capsule containing and preserving in a dry state until used, the chlorides of Ringers solution, a vaso-constricting ingredient and an anaesthetic all in such proportions that when the contents of the capsule are dissolved in the distilled water a solution isotonic to the blood is produced.

10. In combination a sealed glass ampule containing distilled water and a capsule of a material fusible at a point materially below the fusion point of the material of the ampule, said capsule containing and preserving in a dry state until used, the chlorides of Ringers solution, a vaso-constricting ingredient and an anaesthetic all in such proportions that when the contents of the capsule are dissolved in the distilled water a solution isotonic to the blood is produced, said ampule having a breakable neck extcnsion.

11. A hermetically sealed ampule containing distilled water and a capsule of material fusible when the ampule is heated but which solidifies and forms a homogeneous lump in the water when the temperature of the water is reduced, said capsule containing an anaesthetic ingredient which is in predetermined proportions to the amount of water.

12. A hermetically sealed ampule containing distilled water and a capsule of material fusible when the ampule is heated but which solidifies and forms a homogeneous lump in the water when the temperature of the water is reduced, said capsule containing an anaesthetic ingredient which is in predetermined proportions to the amount of water and said ampule having a breakable and reduced neck extension.

13. The herein described medicinal package comprising a sealed container containing two separate ingredients one at least of which is liquid and one of which is separated from the other by a wall fusible at a point materially below the fusion point of the material of the container.

ll. The herein described medicinal package comprising a sealed container containing two separate ingredients one at least of which is a liquid and one of which is separated from the other by being incased within a casing fusible at a point materially below the fusion point of the material of the container.

15. The herein described medicinal package con'iprising a sealed container containing two or more ingredients one at least of which is liquid and one of which is enclosed within a casing fusible at elevated temperature but at a point materially below the fusion point of' the material of the container and non-miscible with the liquid.

16. The herein described medicinal package comprising a sealed container, sealed in vacuo containing two separate ingredients, one at least of which is liquid and one of which is separated from the other by being enclosed within a casing fusible at elevated temperature and non-miscible with the liquid, said casing being fusible at a point materially below the fusion point of the material of the container.

17. A medicinal package comprising a container and two ingredients, therein. which are to be kept separate until the time of use, and a wall of fusible material disposed between said ingredients and separating them, said material being fusible at a point materially below the fusion point of the material of the container.

18. The herein described method of pro ducing fresh sterile solutions which consists of placing some of the ingredients of the solution in a container and there separating them by a Wall of material fusible at a tei'nperature above normal but at a temperature materially below the fusion point of the container so that by subjecting the container to an elevated temperature, the wall may be fused and the ingredients permitted to mix.

in testimony whereof I affix my signature.

ARTHUR E. SMITH. 

